CONFERENCE SERIES: Biological Therapeutic Products

Recorded at: PepTalk: The Protein Science Week

This course provides a detailed look into the discovery, characterization, and manufacturing of Antibody-Drug Conjugates, with a particular focus on safety issues. Featured is an in-depth and extensive case study from Genentech about their use of antibody-drug conjugates in a robust bio-oncology program, including a focus on risk mitigation and risk minimization strategies. This talk is followed by a presentation about Sutro Biopharma's Open Cell Free Synthesis (OCFS) technology for screening, selecting and formulating ADCs. Finally, an excellent overview of the infrastructure required to produce these molecules is presented by Lonza. All three presentations are filled with first-hand insights and practical approaches to successfully developing these potent biologics.

Robert S. Kahn, M.D., CPI, Safety Science Leader, Licensing and Early Development, Global Safety Risk Management, Genentech, a member of the Roche Group

Genentech/Roche has increasing clinical experience in the use of antibody-drug conjugates in a robust bio-oncology development program. Primarily using the Seattle Genetics vc-MMAE platform as well as a linker-DM1 combination developed by ImmunoGen, the molecules to be reviewed during this talk have both common and unique manifestations of toxicity. This talk will outline the current understanding of safety of these molecules and will provide an opportunity to explore risk mitigation and risk minimization strategies which may apply to many ADCs in development.

Discovery, Characterization, and Manufacturing of Next Generation ADC's and Bispecific Antibodies by Cell Free Protein Synthesis

Sutro Biopharma has developed significant improvements and seamless flow in a biologics discovery pipeline for the production of next generation protein therapeutics. Our Open Cell Free Synthesis (OCFS) technology is used in each step of our process, from antibody discovery to HTS screening, pre-clinical protein production, and cGMP manufacturing. Using our OCFS based antibody display technology, we have produced highly diverse antibody libraries that significantly surpass the limits and quality achievable using yeast or phage based display. Selected antibody fragments are reformatted into IgG's prior to rapid, quantitative, HTS screening in OCFS at high antibody titers. Because our protein expression is fully in-vitro, non-natural amino acids can be incorporated for site-specific conjugation of cytotoxic payloads without the high degree of heterogeneity observed using conventional conjugation technologies. Therefore selected antibody fragments can rapidly be reformatted into ADC's as well. Using the company's efficient biochemical protein synthesis platform, ADCs can be prepared in a rapid, parallel manner in several hours at research scale; the linear scalability of the system allows for seamless and prompt scale up of homogenous ADCs for preclinical studies. In addition, because only one protein is made during our production process, expression conditions can be rapidly optimized for traditionally difficult-to-make proteins such as bispecific antibodies and alternative scaffolds. Several case studies will be presented.

This presentation will cover the unique aspects of the raw materials and the supportive analytical and manufacturing infrastructure required for these potent biologics. Bulk drug substance manufacturing process will be discussed along with the typical project timelines and project management challenges.

Speaker Biographies:

Robert S. Kahn, M.D., CPI, Safety Science Leader, Licensing and Early Development, Global Safety Risk Management, Genentech, a member of the Roche Group

Robb Kahn is a Safety Science Leader in the Early Development group of the Global Risk Management Department of Genentech (a member of the Roche Group). Robb's current portfolio of projects includes 9 ADC molecules in early development ranging from pre-IND to phase II clinical trials. He is a member of the Genentech Oncology Clinical Technology and Diagnostics (CTED) Development Team to evaluate novel technologies such as FDG-PET, DCE-MRI and immunoPET imaging in clinical trials. Robb's Industry experience includes Amgen, Sunovion and as a clinical consultant for phase II sites. Robb is the former Medical Director of the 250 bed Charles River Clinical Services Phase 0-II site in the Greater Seattle Area and he has extensive experience as a Principal Investigator for phase 0-II trials. His clinical background includes Pediatric Critical Care, Pediatric and Adult Cardiac and Neurosurgical Anesthesiology, and Interventional Pain Management. He has been board-certified in each of these areas. Robb has been involved in pre-clinical and clinical research areas continuously since 1968.

Chris possesses extensive tactical and strategic experience in creating novel biotherapeutic technology platforms. He is currently Director of Protein Engineering at Sutro Biopharma, a San Francisco biotechnology company focused on the discovery of next generation protein therapeutics for the treatment of cancer. At Sutro, Chris directs efforts focused on the engineering of antibody-drug conjugates, de novo antibody discovery, non-natural amino acid incorporation, and strain engineering. Before Sutro, Chris co-founded Catalyst Biosciences, where he set up the company's protein engineering technology platform, and prior to that, he was a National Cancer Institute Fellow under Professor Jim Wells at Sunesis Pharmaceuticals. He earned a Ph.D. from UCLA in the Dept. of Chemistry and Biochemistry and U.S. Dept. of Energy Laboratory of Structural Biology and Molecular Medicine, where he was an NIH Chemistry / Biology Interface Pre-Doctoral Fellow. He is a named inventor on numerous pending patent applications in protein engineering and biological therapeutics and is the author of multiple peer-reviewed journal articles.

Tom has 27 years of experience in scale-up and manufacturing of biologics. Prior to joining Lonza, he held senior positions in process development and clinical manufacturing at Human Genome Sciences, Otsuka America Pharmaceutical and the National Cancer Institute (NCI) - Frederick Cancer Research Facility. He holds a B.S. in Biochemistry from Shepherd University and an M.S. in Chemical Engineering from the University of Maryland.

About the Conference:

CHI's PepTalk: The Protein Science Week is more than just a conference. It is a community dedicated to the evolving field of biotherapeutics and a gateway to the future of biologics. PepTalk centers around Five Protein related Pipelines: Formulation, Purification, Biotherapeutics, Expression, and Delivery. These synergistic pipelines cover biologics from upstream discovery research to downstream clinical products.